An intrauterine cavity morcellator: A novel approach to high volume uterus morcellation. Ex-vivo study

Objective Uterine size is one of the essential factors determining the feasibility of a minimally invasive gynecologic surgery approach. A traditional electromechanical morcellator is a well-known tool but not without flaws. We aim to assess feasibility and safety of a novel intrauterine power morcellation device for uterine size reduction to overcome these limitations during hysterectomy. Methods This single-arm, observational study was conducted in a single tertiary care medical center from April 2022 to July 2022. Feasibility and safety of a novel intrauterine morcellation device for uterine size reduction was tested in ten post-hysterectomy uteri (Ex-vivo). Measurements and main results Ten uteri were examined in this trial. No major complications occurred during the procedure. All ten (10) uteri were successfully reduced in size (size reduction range was between 9% to 54%). The average resection time using the Heracure Device was 4.3 minutes (range: 1min– 10min). Mean uterus weight reduction was 21%, with a mean circumference reduction of 25%. No leakage was observed from the outer surface of the uterus/serosa after the saline injection post-procedure examination. Conclusion In this novel experiment, we verified the feasibility and safety of the Heracure device for vaginal intra-uterine morcellation for uterine size reduction. This technique could enable rapid and easy removal of the uterus through the vaginal orifice. Clinical trial registration Name of the registry: ClinicalTrials.gov; Number Identifier: NCT05332132.


Study Objective:
The purpose of this feasibility EX-VIVO study is to evaluate the safety and efficacy of the device for vaginal intrauterine cavity morcellation (uterine size reduction) after vaginal/laparoscopic hysterectomy Study Design: Observational Study, Single-arm Study Device: Heracure Device Number of Sites 1

Population
Participants will be recruited from a list of patients consented for hysterectomy with uterus size ≤ 18 weeks. During the procedure, the Heracure System will be used for vaginal uterine size reduction, where the safety & efficacy of the device will be evaluated.

No. of Subjects
Up to 30

Follow Up
Not required

Study Duration
Up to 12 months Procedure:

EX-VIVO Feasibility Study on Extirpated Uteri
The purpose of this feasibility EX-VIVO study is to evaluate the safety and efficacy of the device for vaginal intrauterine cavity morcellation (uterine size reduction).

Study Endpoints
Safety -Serious Adverse Device Effects Procedure Safety will be assessed by recording all the adverse device effects that occur during the treatment with Heracure System. Adverse Event for the ex-vivo study will be defined as uterine perforation at the end of procedure, assessed by inflating the uterus with saline.

Study Secondary Endpoints
Device Success/ Physician satisfaction Defined as ability to reduce uterus size/circumference, and the time required for performing the morcellation procedure

MORCELLATION OF LARGE UTERI
Minimally invasive surgery is commonly used for hysterectomies because of its many benefits over open surgery. Uterine size is one of the major determining factors in selecting the ultimate hysterectomy surgical approach 1 . A measurement of approximately 12 weeks or less usually allows for a vaginal approach [1][2][3][4] . If the estimate of uterine size is larger than 12 weeks, it is likely that the surgeon will choose an abdominal surgical approach. If the uterine size is estimated above 18 weeks, it is almost certain that an abdominal approach will be selected. The abdominal approach is associated with longer hospital stay and recovery time, greater pain, and greater risk of infection, and minimally invasive approaches are associated with shorter lengths of stay and faster recovery times 2,6 . Although small uteri can be removed whole in this approach, larger specimens must be morcellated 1 . Since abdominal morcellation has become controversial recently because of concerns regarding dissemination of occult malignancy and since the current solution of abdominal bag morcellation is cumbersome and time consuming, new techniques that allow surgeons to offer women with large uteri a minimally invasive approach should be investigated and encouraged.

HERA-RS-2000
Heracure System Heracure Medical Ltd., Israel Traceability is established through the use of Lot Numbers for each Finished Device lot.

Intended Use:
Heracure System is intended for use in gynecologic and general surgical endoscopic procedures by trained professional professionals in hospital environments and ambulatory surgery centers.

Device Description
Heracure System consists of the following components:

STUDY DESIGN
The study is designed as an observational study, single-arm study. Any patient who is scheduled for hysterectomy procedure that match the inclusion/exclusion criteria will be offered to give consent.

STUDY OBJECTIVES
The purpose of this feasibility EX-VIVO study is to evaluate the safety and efficacy of the device for vaginal intrauterine cavity morcellation (uterine size reduction) after vaginal/laparoscopic hysterectomy

Primary Endpoints & Success Criteria
Primary Endpoint Test Method

Safety -Serious Adverse Device Effects
Procedure Safety will be assessed by recording all the adverse device effects that occur during the treatment with Heracure System. Adverse Event for the ex-vivo study will be defined as uterine perforation at the end of procedure, assessed by inflating the uterus with saline. In order to minimize the interference with the hospital routine pathology analysis of uterus, an endometrial biopsy ("Pipelle") will be performed prior to the hysterectomy procedure to enable the data for ruling out endometrial pathology, such as hyperplasia or carcinoma.

10.2.2.3
The purpose of this feasibility EX-VIVO study is to evaluate the safety and efficacy of the device for intrauterine cavity morcellation (e.g., reducing uterine size from the inside of the uterine cavity). During the morcellation procedure, a protective barrier will be wrapped around the uterus.

10.2.2.4
The size of the uterus (e.g., circumference, weight) shall be recorded before and after the morcellation procedure, as well as the total resection time.
10.2.2.5 To assess uterine perforation at the end of procedure, the uterus shall be inflated with saline and observed for leakage.
10.2.2.6 At the end of the procedure, the entire uterus and its resected tissue will be sent to pathology for hospital routine pathology analysis.

DURATION OF STUDY
Study duration up to 12 months

RISK ANALYSIS
The risks related to the investigational procedure are mitigated by: 12.1 Inclusion/Exclusion Criteria, which are provided in Section 9 of this protocol.
12.2 Consistent with the current hospital protocol, after completing the testing, all samples will be returned to pathology, where routine pathological analysis will be conducted. In the case that the pathologist on site is identifying an abnormal appearance of the uterine tissue, study will be discontinued, and samples will be sent to pathology, where routine pathological analysis will be conducted.

MANAGEMENT OF ADVERSE EVENTS
13.1 An adverse event is any undesirable or unintentional event that occurs during the course of the study, considered related to Heracure device. Regardless of severity or relationship to the investigational device, all adverse events occurring during the study must be recorded in the patient's CRF.
13.2 Due to the nature of the current study performed on ex-vivo extirpated uterus (no patient is involved), an adverse event will be defined in the study as uterine perforation at the end of procedure, assessed by inflating the uterus with saline, or any event that leads to interference with the hospital routine pathology analysis of the uterus post procedure.

Declaration of Helsinki
The study will be conducted according to the guidelines established in the Declaration of Helsinki, ICH E-6 GCP Guidelines and ISO 14155 requirements.

Reasons for removing a patient from the ex-vivo study
• Patients who express a desire to withdraw from the study.
• Any medical condition that, in the opinion of the investigator, warrants discontinuation from the study.
• In the case that the pathologist on site is identifying an abnormal appearance of the uterine tissue, study will be discontinued, and samples will be sent to pathology.

PUBLICATION POLICY
18.1 Heracure Medical recognizes that the availability of study results is important to the communication of significant new information for the medical profession, patients and the general public. Such communication includes publication of a paper in a peer-reviewed medical journal, abstract submission with a poster or oral presentation at a scientific meeting, or making study results public by some other means.
18.2 Heracure Medical designs and conducts, together with the Investigators, studies in an ethical and scientifically rigorous manner to determine the benefits, risks, and value of medical device products. As Sponsor of such studies, Heracure Medical receives from the Investigators at all research sites, and subsequently verifies, the data for the studies it conducts. As owners of that data, Heracure Medical works diligently with the Investigators to ensure the accuracy and integrity of the entire study database.

ADMINISTRATIVE PROCEDURES OF THE INVESTIGATION:
Investigator sites and study documentation may be subject to Quality Assurance audits during the course of the study. In addition, inspections may be conducted by regulatory bodies at their discretion, during and after study completion.

STATISTICAL ANALYSIS
Descriptive statistics will be provided.

CONFIDENTIALITY
The subject's name and personal data will remain confidential and will not be published in any way. Patients will be identified on all CRFs by a unique reference number. CRFs are confidential documents. The sponsor's monitor or representative and regulatory representatives, auditors and inspectors may have access to medical files in order to verify authenticity of data collected. Accordingly, data will only be available to the sponsor, the Investigator, Investigators' staff, the investigation statistician, and if requested to the advisory committee and regulatory authorities. The Investigator will maintain as part of the investigation file a list identifying all patients entered into the study.